Prescribing for Pregnant or Lactating Women

Transcription

1 Disclosure Statement Dr. Jankowski has no financial relationships with any commercial interests. March, 2013 RoseAnn L. Jankowski, Pharm.D. Educational Objectives At the conclusion of this educational activity, participants should be able to: describe the FDA Risk Factor ategories. outline and discuss general considerations for increasing the safety of medications prescribed for women who are pregnant or breastfeeding an infant. state the pregnancy and lactation status of medications commonly prescribed under the optometrist scope of practice. Introduction: Why is this information important? Two patient groups requiring special consideration by optometrists when prescribing topical or oral (systemic) medications are women who are pregnant and women who are breastfeeding an infant. Many optometrists have had minimal training in specifically prescribing for these patient groups risk factor ratings can be difficult to quickly locate and to interpret Fewer studies have been done and less is generally known about drug use while breastfeeding than when using medications during pregnancy. Introduction: Why is this information important? There is sometimes a mistaken impression that drugs administered topically in the eye are not absorbed systemically and never present a potential risk to the fetus or infant when used by a woman who is pregnant or breastfeeding Nearly all therapeutic drugs administered to or taken by a woman who is pregnant can cross the placenta. Depending on pharmacologic factors and drug properties, drugs that cross the placenta can reach different concentrations in the developing fetus. This includes ophthalmic medications. Prescribing onsiderations for Women Who Are Pregnant The major factor contributing to the concentration of drug in the fetus is the concentration of drug present in the mother. Other contributing factors include: - gestational age of the fetus - the degree of placental development (placental blood flow volume and surface area) - drug molecular size - lipid solubility of the drug - protein binding characteristics of the drug - degree of drug ionization in the environment of physiologic ph 1

2 Prescribing onsiderations for Women Who Are Pregnant Teratogenic effects resulting in fetal malformations are known to be both: - dose related (how much drug) - time related (when, and for how long the drug exposure occurs) The period of greatest risk for malformations to occur or originate is within the first three months of gestation, however anatomic, functional or behavioral effects can occur throughout the entire gestational period. Prescribing onsiderations for Women Who Are Pregnant Teratogenic effect studies conducted in animals may not always be directly relatable to potential effects in humans. Studies conducted in humans often cannot fully address all possible areas or types of human risk, including genetic differences in populations. Other specific risk factor elements include - dose-related effects - the pharmacokinetic properties of each drug - potential maternal or fetal disease states - the specific stage of pregnancy involved - the timing of drug exposure - the degree of drug exposure over time. Prescribing onsiderations for Women Who Are Pregnant To best address all of these potential concerns, recommendations for drug use during pregnancy are often criteria-based using data and results from available studies. These criteria often include: - what (if any) information is known from studies conducted in humans and/or animals - if the nature of the study data is limited or extensive - whether the data is suggestive of risk (and if so, if the risks would be considered to be low, moderate, or high) - whether the data indicates any trimester-specific findings or cautions - whether any results suggest that a drug should be considered contraindicated for use during pregnancy. Prescribing onsiderations for Women Who Are Pregnant One of the most common criteria-based systems describing potential drugrelated fetal risk is the Risk Factor rating assigned by the U.S. Food and Administration (FDA). These rating categories relate to risk factors which are assigned based on the level of known risk that each drug presents to the fetus. While the assigned risk factor rating can assist a prescriber in an initial determination of safety for the fetus, the rating should be considered as a starting point only. NOTE: - FDA Risk Factors do NOT include lactation risks. - Not all currently available drugs have ratings. Prescribing onsiderations for Women Who Are Pregnant FDA PREGNANY RISK FATOR ATEGORIES ased on submitted clinical study information reviewed as part of the drug approval process, the Food and Administration (FDA) assigns one of five pregnancy risk factors based on the degree of risk that use of the drug would potentially cause to the fetus. ategory A ategory ontrolled studies in pregnant women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote. Either animal-reproduction studies have not demonstrated fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters.) Prescribing onsiderations for Women Who Are Pregnant FDA PREGNANY RISK FATOR ATEGORIES ategory Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. s should be given only if the justifies the potential risk to the fetus. ategory D ategory X There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a lifethreatening situation or for a serious disease for which safer drugs cannot be used or are ineffective.) Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly any possible benefit. The drug is contraindicated in women who are or may become pregnant. 2

3 Prescribing onsiderations for Women Who Are Pregnant Reviewing the FDA Risk Factor rating does not address the safety of using the drug while breast-feeding, and should be followed by the prescriber considering other important factors such as: - gestational stage - more detailed risk information - individual factors such as other medical conditions that the mother may have. The EST use of FDA Risk Factor ratings would be for the optometrist to contact the physician directly supervising the patient s pregnancy to discuss the rating and the advisability of proceeding with the proposed therapy given the patient s stage of pregnancy, general health, etc. Prescribing onsiderations for Women Who Are linical information concerning the safety of drug use while breast-feeding an infant is often more limited than information regarding the safe use of drugs during pregnancy. Many published studies of drug use during lactation have been conducted in animals. omparisons between accumulated drug concentrations in animals can be difficult to make with certainty in humans. This difficulty arises because of significant differences which exist between the compositions of breast milk between different species. Prescribing onsiderations for Women Who Are Studies have also indicated that drug concentration in breast milk can also be affected by drug characteristics including lipid solubility, protein binding ability, and degree of ionization. Also complicating assessments of safety is the overall lack of definitive information on manifested or measured pharmacologic effects in infants when drugs have been ingested through General and Lactation for s Under the Optometry Scope of Practice Relative recommendations and cautions regarding drug use while breastfeeding can be found in medical literature, however prescribers are always advised to conduct a risk to benefit assessment and to seek the advice or opinion of the physician directly supervising the patient s post-natal care prior to prescribing medications to women who are breastfeeding an infant. Prescribers should look for breastfeeding compatibility ratings from the American Academy of Pediatrics (AAP). Fluorescein Fluorexon Lissamine Green Rose engal ategory No reports of fetal complications during pregnancy. No US FDA rating is available. No US FDA rating is available. No US FDA rating is available. Is excreted in breast milk, use with caution in a lactating woman. Unknown if drug No information No information omments Use in the eye produces measurable amounts in systemic circulation. Expect transmission to the fetus. can cause fetal harm. Little information available. Use only when clearly indicated. Little information available. Use only when clearly indicated. Proparacaine Lidocaine Tetracaine ategory Safe use not established Use not associated with any risks, but caution should be used. Should be used only if the justifies the potential risk to the fetus. No information, safe use not established. AAP Rating: Maternal medication usually WHO: ompatible with breast feeding. omments benefits outweigh potential risks. Local anesthetics generally cross into breast milk, concentrations usually 40% of serum levels. Low molecular wt. suggests drug can cross the placenta and will be excreted into 3

4 Phenylephrine Atropine, Homatropine yclopentolate ategory Safe use has not been established. clearly needed and Safe use has not been established. clearly needed. Safe use has not been established. clearly needed. May be detectable in breast milk, but AAP lists these drugs as being omments ategory Tropicamide potential benefit Use only if potential benefit omments ategory Naphazoline Inconclusive information at this time. Oxymetazoline No US FDA rating is available. Unknown Phenylephrine Inconclusive information at this time. Tetrahydrozoline No US FDA rating is available. Inconclusive information at this time. omments benefits outweigh potential risks. Safe use for pregnancy or in lactation is not known. benefits outweigh potential risks. Safe use for pregnancy or in lactation is not known. Azelastine (Optivar ) A/MS romolyn (rolom, Opticrom ) MS Emedastine (Emadine ) A Epinastine (Elestat ) A/MS ategory clearly needed. clearly needed. is is is milk after topical use. crosses into human Exercise caution during omments Teratogenic effects in mice at high levels noted. Animal studies showed some effects at higher than human doses. Ketotifen (Alaway, Zaditor ) A/MS Lodoxamide (Alomide ) MS Nedocromil (Alocril ) MS Alcaftadine (Lastacaft ) A/MS ategory clearly needed. clearly needed. clearly needed. crosses into Exercise caution during crosses into omments Animal studies showed some effects at higher than human doses. during lactation Olopatadine (Patanol, Pataday ) A/MS Pemirolast (Alamast ) MS epotastine (epreve ) A/MS ategory crosses into crosses into Exercise caution during crosses into Exercise caution during omments Animal studies showed some effects at higher than human doses. Animal studies showed some effects at higher than human doses. 4

5 Dexamethasone Difluprednate (Durezol ) ategory benefits to the mother outweigh risks benefits to the mother outweigh risks Sources recommend that a decision should be made to discontinue nursing or discontinue the drug. Unknown whether topical drug is excreted into omments Topically applied steroids are absorbed systemically. Topically applied steroids are absorbed systemically. (Note: Ophthalmic prednisolone products are all ategory, with no known lactation information.) Fluorometholone (FML, Flarex ) Loteprednol (Lotemax, Alrex ) ategory benefits to the mother outweigh risks benefits to the mother outweigh risks Sources recommend that a decision should be made to discontinue nursing or discontinue the drug. Unknown whether topical drug is excreted into omments Rimexolone (Vexol ) romfenac (Xibrom ) Flurbiprofen (Ocufen ) ategory benefits to the mother outweigh risks Use should be avoided during late pregnancy due to potential fetal cardiac risk Sources recommend that a decision should be made to discontinue nursing or discontinue the drug. omments Diclofenac (Voltaren ) Nepafenac (Nevanac ) ategory Molecular weight low enough that excreted into breast milk should be expected. Infant risk cannot be omments Although one source lists diclofenac as being compatible with breast feeding, caution during lactation should still be exercised. Ketorolac (Acular, Acular LS ) ategory the potential benefit justifies the potential risk to the fetus. Use should be avoided during late pregnancy due to cardiac risk when considered for use during breast feeding. omments in using this drug especially during pregnancy. yclosporine (Restasis ) ategory Administer during very clearly needed. Oral cyclosporine milk, but no definitive safety recommendation is currently available for topically applied drug. omments in using this drug 5

6 Dipivefrin (Propine ) Apraclonidine (Iopidine ) rimonidine (Alphagan P ) ategory omments pregnancy and potential fetal/infant risks. pregnancy and potential fetal/infant risks. Echothiophate (Phospholine Iodide ) Pilocarpine (Isoptoarpine ) ategory ecause of potential for serious effects in nursing infants, a decision should be made to discontinue drug or discontinue nursing. is expected to cross into omments etaxolol (etoptic ) arteolol (Ocupress ) Levobunolol (etagan ) ategory omments risk risk Metipranolol (Optipranolol ) Timolol (Timoptic ) ategory is detectable in human milk after ophthalmic administration. Infant risk is possible. omments ecause of potential for serious effects in nursing infants, a decision should be made to discontinue drug or discontinue nursing. Acetazolamide (Diamox ) rinzolamide (Azopt ) ategory The AAP states that the drug is is Infant risk cannot be omments ecause of potential for serious effects in nursing infants, a decision should be made to discontinue drug or discontinue nursing. Dorzolamide (Trusopt ) Methazolamide (Neptazane ) ategory pregnancy only if potential benefit risk. is Infant risk cannot be is Infant risk cannot be omments ecause of potential for serious effects in nursing infants, a decision should be made to discontinue drug or discontinue nursing. 6

7 Latanoprost (Xalatan ) imatoprost (Lumigan, Latisse ) Travoprost (Travatan ) ategory omments Travoprost may interfere with maintenance of pregnancy, so is not recommended for use during pregnancy or by women attempting to become pregnant. Tafluprost (Zioptan ) ategory omments Aspirin Acetaminophen Ibuprofen ategory D Studies have indicated a risk to the fetus. crosses the placenta, considered safe for use at therapeutic doses for short periods of time. early, D later Studies have indicated a risk to the fetus. The AAP states that aspirin should be given with caution during known to cross into human breast milk, but AAP states that it is The AAP states that the drug is omments Probably safest to avoid use during pregnancy or Safer to avoid during pregnancy. Naproxen ategory early, D later Studies have indicated a risk to the fetus. The AAP states that the drug is odeine The AAP states that the drug is breastfeeding, but caution still needed. Hydrocodone Hydrocodonecontaining analgesics can be ategory or D depending on prolonged use or high doses near term. Available evidence lacking to confirm safety while omments aution in pregnancy and during lactation if long-term or high doses used; particularly at term. potential risk to infant. Acyclovir (Zovirax ) Valacyclovir (Valtrex ) Famciclovir (Famvir ) ategory easily crosses the placenta. Transmission to fetus assumed due to low MW of drug. AAP lists the drug as being compatible with Appears to be No lactation studies have confirmed safety, use during breastfeeding is not recommended. omments Most human pregnancy experience with this drug compared to valacyclovir or famciclovir. Prodrug of acyclovir Natamycin (Natacyn ) ategory Unknown if the drug crosses the placenta, but topically applied drug known to cross into systemic circulation in low amounts. is Infant risk cannot be omments The manufacturer recommends that the drug only be prescribed for use in pregnant women when clearly needed and the potential benefits are determined to justify potential risk to the fetus. Trifluridine (Viroptic ) fetal risk No available reports relating to Not recommended during lactation unless potential benefits justify potential risks. 7

8 Amoxicillin (Amoxil ) Amoxicillin/ lavulanate (Augmentin ) Ampicillin (Principen ) ategory AAP classifies the drug as being omments Effects in breastfed infant are possible 1. Effects on infant unknown. Effects in breastfed infant are possible 1. AAP classifies the drug as being Penicillin VK AAP classifies the drug as being Dicloxacillin (Dynapen ) Probably excreted into breast milk in low concentrations, usually considered Effects in breastfed infant are possible 1. Effects in breastfed infant are possible 1. Effects in breastfed infant are possible 1. lindamycin (leocin ) ategory AAP classifies the drug as being compatible with acitracin No information on ophthalmic use. Sulfonamides s in this group have a rating of. SMX/TMP also has a rating. Risks not thought to be high for healthy infants, but can be problematic for infants with health problems or prematurity. SMX/TMP may be breastfeeding in a healthy infant. omments s known to cross the placenta, particular risks exist in the third trimester as neonate could develop jaundice, kernicterus, and hemolytic anemia. 1 Altered GI flora, inducing allergy/sensitivity, alteration of & S results efadroxil (Duricef ) ategory AAP classifies the drug as being compatible with efprozil (efzil ) AAP classifies the drug as being compatible with efuroxime (Zinacef, eftin ) ephalexin (Keflex ) omments esifloxacin (esivance ) iprofloxacin (iloxan ) Gatifloxacin (Zymaxid ) Levofloxacin (Iquix, Quixin ) All oral fluoroquinolones are ategory ategory Unknown if drug is milk AAP classifies drug as being breastfeeding Excretion into breast milk not confirmed, but likely. aution recommended. Known to be excreted into omments Infant risk during lactation cannot be Effects of exposure to breastfed infant unknown. Effects of exposure to breastfed infant unknown. A causal relationship with birth defects has not been able to be ruled out with FQs: study data suggests low risks with some FQs, other data has indicated potential increased risk during the first trimester for some FQs, and other studies have concluded that use of these drugs should be avoided if possible during pregnancy. Moxifloxacin (Vigamox, Moxeza ) Ofloxacin (Ocuflox ) ategory Excretion into breast milk not confirmed, but likely. aution recommended. AAP classifies drug as being breastfeeding omments Effects of exposure to breastfed infant unknown. Azithromycin (Z-Pak, Azasite ) larithromycin (iaxin ) Erythromycin (Excluding erythromycin estolate) ategory, however DO NOT prescribe estolate form to pregnant patients. Oral form excreted into breast milk, no data on topical form. Not known but expected to be Use caution until more data is available. AAP classifies erythromycins (except estolate form) to be omments Effects of exposure to breastfed infant unknown, more data is needed to fully confirm safety. 8

9 Gentamicin (Garamycin, Genoptic ) Tobramycin (Tobrex ) Neomycin (in combination with other antiinfective agents ategory Usually ; check for individual products AAP classifies drug as being breastfeeding Is milk, not recommended for use No consistent data but minimal excretion into breast milk is likely. omments No data on safety Tetracycline (Sumycin ) Doxycycline (Vibramycin ) ategory D Many sources recommend avoiding use entirely during pregnancy D Many sources recommend avoiding use entirely during pregnancy Is Is omments Summary Recommendations for Optometrists Always treat and prescribe collaboratively with the physician who is supervising the patient s pregnancy or breastfeeding period. - onsult with this physician regarding the eye condition, and the drug or drugs that are under consideration for use. Specifically discuss the advisability of starting the intended course of therapy before prescribing for the patient, and document the conversation and conclusions in the medical record. onsulting with the patient s physician and a pharmacist can be helpful in determining when it is safe to resume nursing an infant if breastfeeding was temporarily discontinued while completing a course of therapy. Summary Recommendations for Optometrists Assess whether use of routine office medications (dyes, dilating drugs, local anesthetics, etc.) are necessary for patients who are pregnant or breastfeeding an infant. Wherever possible, check with the patient s physician and review available current clinical data in advance. Use effective but not excessive anti-infective doses for as short a period of time as possible, and conduct culture and sensitivity tests when treating eye infections in patients who are pregnant or lactating. ( & S results will not only assist in confirming that the prescribed therapy will be effective, but will also assist in possibly identifying other efficacious anti-infective agents which may have better Risk Factor ratings and/or breastfeeding safety profiles.) Summary Recommendations for Optometrists Recommend use of nasolacrimal occlusion to minimize systemic absorption when administering topical ophthalmic medications. heck or obtain assistance in checking the most recent authoritative sources of teratogenicity, pregnancy risk, and lactation risk information prior to prescribing. This information can be provided by obstetricians, pediatricians, drug information centers, many drug information databases, and pharmacists. Optometrists who work collaboratively with the physician who is supervising the pregnancy or breastfeeding period of a patient requiring medication therapy, and who follow prudent recommendations for drug selection and use will provide the greatest margin of safety for the developing fetus or newborn infant. Follow the patient very closely, and stress the importance of keeping all medical appointments during pregnancy and while nursing an infant. 9

10 Post-activity questions 1. Which of the following Risk ategories assigned by the FDA to a new drug would indicate that the drug should be considered contraindicated for use during pregnancy? a.) ategory X b.) ategory D c.) ategory d.) ategory Post-activity questions 2. Which of the following steps can be recommended and taught to patients who are pregnant in order to minimize systemic absorption of ophthalmic anti-infective agents? a.) using nasolacrimal occlusion after instilling anti-infective eye drops b.) looking up Risk ategories on the FDA web site c.) using antibiotic drops around the clock instead of during waking hours only d.) placing lubricating ophthalmic ointment in the eye just before the anti-infective drops are instilled. Post-activity questions 3. Which of the following drugs is generally considered safe to use during pregnancy and while breast-feeding? a.) doxycycline b.) cephalexin c.) neomycin d.) clarithromycin Post-activity questions 4. An optometrist has diagnosed bacterial conjunctivitis in a 28 year-old woman who is in her first trimester of pregnancy. Which of the following actions of the optometrist would provide the GREATEST margin of safety for the developing fetus? a.) Advise that the patient avoid breast-feeding to avoid transmitting any residual prescribed antibiotic drug after the infant is born. b.) onsider use of ophthalmic natamycin only to treat bacterial infections of the eye in patients who are in the first or second trimester of pregnancy. c.) all the patient s obstetrician to discuss the advisability of using the intended antibiotic prior to issuing a prescription for the drug to the patient. d.) Use only antibiotic agents that have a Risk ategory rating of or D in this patient. 10